神经系统课件：抗帕金森病药.pptVIP

Neurodegenerative Diseases Parkinson’s disease Alzheimer’s disease（阿尔茨海默病, AD） Huntington disease（亨廷顿病, HD） Amyotrophic lateral sclerosis（肌萎缩侧索硬化症, ALS） * Anti-Parkinson Drugs 抗帕金森病药物 * The nervous disorder characterized by Dr. James Parkinson（1817） Resting tremor (静止性震颤) Rigidity (肌强直) Bradykinesia (运动迟缓) Dementia (痴呆) Excessive salivation * Parkinson’s disease (帕金森病，PD) 多巴胺（DA）缺失假设 PD患者黑质病变，DA合成减少，使纹状体内DA含量降低，导致黑质-纹状体通路DA能神经功能减弱，胆碱能神经功能占优势，引起肌张力增高等症状 * 发病机制 依据： 左旋多巴或DA激动剂可显著缓解PA症状； 破坏黑质-纹状体DA神经元的神经毒素和长期使用DA阻断剂可PA。致PA。 Pathogenesis Progressive degeneration of DA-producing neurons in the substantia nigra (黑质) Imbalance in DA and ACh action on neurons of the corpus striatum (纹状体) * 黑质 纹状体 侧脑室 * * Pathological Hallmark Abnormal accumulation of the ?-synuclein protein（?-突触核蛋白） in the brain. ?-突触核蛋白? Lewy body * Therapeutic Strategies Increase DA activity or reduce ACh activity, restore their balance in the corpus striatum At present, there is no cure for PD, but medications, surgery and multidisciplinary management can provide relief from the symptoms. * Levodopa (左旋多巴, L-dopa) Has been the most widely used treatment for over 30 years. L-dopa is transformed into DA in the dopaminergic neurons by dopa-decarboxylase (多巴脱羧酶) to restore DA activity in the corpus striatum. * Is absorbed rapidly from the intestine and enter the CNS to become DA 95%在外周被脱羧酶脱羧 ? DA 仅1-3%的原形药物可到达脑内 外周脱羧酶抑制药显著增加原形药物透过BBB Is usually administered with peripheral dopa decarboxylase inhibitors * Pharmacokinetics Reduce required dosage and toxicity Sinemet (心宁美)： carbidopa (卡比多巴)/L-dopa =1:10 Madopar (美多巴 ) ： benserazide (苄丝肼)/L-dopa =1:4 * L-dopa + peripheral dopa decarboxylase inhibitors * Fate of orally administered L-dopa and the effect of carbidopa. Therapeutic Effects Ameliorates all PD symptoms after several weeks of treatment and improves life quality Is particularly effective in relieving bradykinesia (运动迟缓) In combination with carbidopa to reduce dosage and toxi